Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingency

  1. Richard B Crouse
  2. Kristen Kim
  3. Hannah M Batchelor
  4. Eric M Girardi
  5. Rufina Kamaletdinova
  6. Justin Chan
  7. Prithviraj Rajebhosale
  8. Steven T Pittenger
  9. Lorna W Role
  10. David A Talmage
  11. Miao Jing
  12. Yulong Li
  13. Xiao-Bing Gao
  14. Yann S Mineur
  15. Marina R Picciotto  Is a corresponding author
  1. Yale University, United States
  2. NIH, United States
  3. Chinese Institute for Brain Research, China
  4. Peiking University, China
  5. Yale University School of Medicine, United States

Abstract

The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and activity of neurons expressing CaMKIIα (a marker for glutamatergic principal cells) in mice during cue-reward learning using a fluorescent ACh sensor and calcium indicators. We found that ACh levels and nucleus basalis of Meynert (NBM) cholinergic terminal activity in the BLA (NBM-BLA) increased sharply in response to reward-related events and shifted as mice learned the cue-reward contingency. BLA CaMKIIα neuron activity followed reward retrieval and moved to the reward-predictive cue after task acquisition. Optical stimulation of cholinergic NBM-BLA terminal fibers led to quicker acquisition of the cue-reward contingency. These results indicate BLA ACh signaling carries important information about salient events in cue-reward learning and provides a framework for understanding how ACh signaling contributes to shaping BLA responses to emotional stimuli.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all experiments on Dryad Digital Repository: doi:10.5061/dryad.3xsj3txcf

The following data sets were generated

Article and author information

Author details

  1. Richard B Crouse

    Interdepartmental Neuroscience Program, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9509-9263
  2. Kristen Kim

    Interdepartmental Neuroscience Program, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Hannah M Batchelor

    Interdepartmental Neuroscience Program, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Eric M Girardi

    Psychiatry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Rufina Kamaletdinova

    Psychiatry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3650-8207
  6. Justin Chan

    Psychiatry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Prithviraj Rajebhosale

    NINDS, NIH, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9893-3025
  8. Steven T Pittenger

    Psychiatry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Lorna W Role

    NINDS, NIH, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5851-212X
  10. David A Talmage

    NIMH, NIH, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Miao Jing

    Chinese Institute for Brain Research, Chinese Institute for Brain Research, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Yulong Li

    School of Life Sciences, Peiking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Xiao-Bing Gao

    Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Yann S Mineur

    Psychiatry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Marina R Picciotto

    Psychiatry, Yale University, New Haven, United States
    For correspondence
    marina.picciotto@yale.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4404-1280

Funding

National Institute on Drug Abuse (DA14241)

  • Richard B Crouse
  • Kristen Kim
  • Hannah M Batchelor
  • Rufina Kamaletdinova
  • Justin Chan
  • Steven T Pittenger
  • Yann S Mineur
  • Marina R Picciotto

National Institute on Drug Abuse (DA037566)

  • Richard B Crouse
  • Kristen Kim
  • Hannah M Batchelor
  • Rufina Kamaletdinova
  • Justin Chan
  • Steven T Pittenger
  • Yann S Mineur
  • Marina R Picciotto

National Institute of Mental Health (MH077681)

  • Richard B Crouse
  • Kristen Kim
  • Hannah M Batchelor
  • Rufina Kamaletdinova
  • Justin Chan
  • Steven T Pittenger
  • Yann S Mineur
  • Marina R Picciotto

National Institute of Neurological Disorders and Stroke (NS022061)

  • Prithviraj Rajebhosale
  • Lorna W Role
  • David A Talmage

National Institute of Mental Health (MH109104)

  • Prithviraj Rajebhosale
  • Lorna W Role
  • David A Talmage

National Institute on Drug Abuse (DA046160)

  • Xiao-Bing Gao

National Institute of Neurological Disorders and Stroke (Intramural)

  • Prithviraj Rajebhosale
  • Lorna W Role

National Institute of Mental Health (Intramural)

  • Prithviraj Rajebhosale
  • David A Talmage

National Institute of Neurological Disorders and Stroke (T32-NS007224)

  • Richard B Crouse

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Matthew N Hill, University of Calgary, Canada

Ethics

Animal experimentation: All procedures were approved by the Yale University Institutional Animal Care & Use Committee in compliance with the National Institute of Health's Guide for the Care and Use of Laboratory Animals. (protocol: 2019-07895)

Version history

  1. Received: March 27, 2020
  2. Accepted: September 17, 2020
  3. Accepted Manuscript published: September 18, 2020 (version 1)
  4. Accepted Manuscript updated: September 22, 2020 (version 2)
  5. Version of Record published: October 1, 2020 (version 3)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Richard B Crouse
  2. Kristen Kim
  3. Hannah M Batchelor
  4. Eric M Girardi
  5. Rufina Kamaletdinova
  6. Justin Chan
  7. Prithviraj Rajebhosale
  8. Steven T Pittenger
  9. Lorna W Role
  10. David A Talmage
  11. Miao Jing
  12. Yulong Li
  13. Xiao-Bing Gao
  14. Yann S Mineur
  15. Marina R Picciotto
(2020)
Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingency
eLife 9:e57335.
https://doi.org/10.7554/eLife.57335

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https://doi.org/10.7554/eLife.57335

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